Glycolytic oscillations in isolated rabbit ventricular myocytes.
Previous studies have shown that glycolysis can oscillate periodically, driven by feedback loops in regulation of key glycolytic enzymes by free ADP and other metabolites. Here we show both theoretically and experimentally in cardiac myocytes that when the capacity of oxidative phosphorylation and the creatine kinase system to buffer the cellular ATP/ADP ratio is suppressed, glycolysis can cause large scale periodic oscillations in cellular ATP levels (0.02-0.067 Hz), monitored from glibenclamide-sensitive changes in action potential duration or intracellular free Mg2+. Action potential duration oscillations originate primarily from glycolysis, since they 1) occur in the presence of cyanide or rotenone, 2) are suppressed by iodoacetate, 3) are accompanied by at most very small mitochondrial membrane potential oscillations, and 4) exhibit an anti-phase relationship to NADH fluorescence. By uncoupling energy supply-demand balance, glycolytic oscillations may promote injury and electrophysiological heterogeneity during acute metabolic stresses, such as acute myocardial ischemia in which both oxidative phosphorylation and creatine kinase activity are inhibited.
Yang
Jun-Hai
JH
Cardiovascular Research Laboratory, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California 90095-1760, USA.
Yang
Ling
L
Qu
Zhilin
Z
Weiss
James N
JN
D000200:Action Potentials; D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D003402:Creatine Kinase / Q000378:metabolism; D003486:Cyanides / Q000494:pharmacology; D006019:Glycolysis; D006352:Heart Ventricles / Q000378:metabolism; D007461:Iodoacetates / Q000494:pharmacology; D008564:Membrane Potentials; D032342:Muscle Cells / Q000378:metabolism*; D009243:NAD / Q000737:chemistry; D009991:Oscillometry; D010766:Phosphorylation; D011817:Rabbits; D012402:Rotenone / Q000494:pharmacology
D003486:Cyanides; D007461:Iodoacetates; D012402:Rotenone; D009243:NAD; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D003402:Creatine Kinase